The projects described in this proposal are designed to evaluate the role of fetal brain tissue transplants in mediating functional recovery from traumatic injuries to the central nervous system. Using behavioral, anatomical and electrophysiological techniques, this project will examine whether: (a) the effectiveness of transplants in promoting behavioral recovery varies as a function of the time between the initial brain injury and the introduction of the fetal tissue into the host brain; (b) "recovered" behaviors are different than those used by intact animals--(i.e., is there restitution or substitution of behavioral functions induced by transplant surgery?); (c) the effectiveness of fetal brain tissue transplants can be enhanced by incubation in neurotrophic substances prior to implantation in the damaged host brain; (d) specificity of tissue between fetal tissue and host is an essential condition for obtaining functional recovery (e.g., can embryonic frontal cortex assist in facilitating behavioral recovery following occipital cortex lesions?); (e) interspecies transplants are effective in promoting functional recovery (e.g.,, can embryonic cortical tissue taken from the hamster be used to reduce lesion-induced, cognitive deficits in adult rats?); (f) specific anatomical connections formed between the host brain and the transplant material are necessary to mediate functional recovery. Although there are a number of new and exciting approaches to the study of neural plasticity, it is surprising how few are concerned with detailed analysis of the behavioral consequences of injury-induced changes in C.N.S. functions. Yet, understanding how the nervous system mediates, or can be induced to mediate, behavioral and functional recovery is the key issue for those faced with the prospect of treating the more than 400,000 patients who suffer severe C.N.S. injuries in this country each year. Any attempts to develop specific, effective and long-lasting treatments for the victims of brain and spinal cord injuries, should be given some attention. This proposal addresses the question of whether fetal brain cells can serve as one form of therapy for severe brain dysfunctions. Careful behavioral analyses, using complex learning tasks are followed by detailed electrophysiological and anatomical assays of the transplant effects. The long-term goals of this research are to find the means to alleviate some of the suffering caused by C.N.S. injuries and restore the patient to a more normal life.